Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Weill Medical College, Cornell University, New York, New York, USA.
J Infect Dis. 2020 Sep 1;222(7):1180-1187. doi: 10.1093/infdis/jiaa237.
We report on predictors of adenovirus (ADV) viremia and correlation of ADV viral kinetics with mortality in ex vivo T-cell depleted (TCD) hematopoietic cell transplant (HCT).
T cell-depleted HCT recipients from January 1, 2012 through September 30, 2018 were prospectively monitored for ADV in the plasma through Day (D) +100 posttransplant or for 16 weeks after the onset of ADV viremia. Adenovirus viremia was defined as ≥2 consecutive viral loads (VLs) ≥1000 copies/mL through D +100. Time-averaged area under the curve (AAUC) or peak ADV VL through 16 weeks after onset of ADV viremia were explored as predictors of mortality in Cox models.
Of 586 patients (adult 81.7%), 51 (8.7%) developed ADV viremia by D +100. Age <18 years, recipient cytomegalovirus seropositivity, absolute lymphocyte count <300 cells/µL at D +30, and acute graft-versus-host disease were predictors of ADV viremia in multivariate models. Fifteen (29%) patients with ADV viremia died by D +180; 8 of 15 (53%) died from ADV. Peak ADV VL (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.52-3.33) and increasing AAUC (HR, 2.95; 95% CI, 1.83-4.75) correlated with mortality at D +180.
In TCD HCT, peak ADV VL and ADV AAUC correlated with mortality at D +180. Our data support the potential utility of ADV viral kinetics as endpoints in clinical trials of ADV therapies.
我们报告了腺病毒 (ADV) 血症的预测因素,以及体外 T 细胞耗竭 (TCD) 造血细胞移植 (HCT) 中 ADV 病毒动力学与死亡率的相关性。
2012 年 1 月 1 日至 2018 年 9 月 30 日期间,前瞻性监测 TCD HCT 受者的 ADV 血浆,直至移植后 100 天(D+100)或 ADV 血症发作后 16 周。ADV 血症定义为 D+100 时有≥2 次连续病毒载量(VL)≥1000 拷贝/ml。通过 Cox 模型探索 ADV 血症发作后 16 周的平均时间曲线下面积(AAUC)或 ADV 峰值 VL 作为死亡率的预测因素。
在 586 例患者(成人 81.7%)中,有 51 例(8.7%)在 D+100 时发生 ADV 血症。年龄<18 岁、受者巨细胞病毒血清阳性、D+30 时绝对淋巴细胞计数<300 个/µL 和急性移植物抗宿主病是 ADV 血症的多变量模型预测因素。15 例(29%)有 ADV 血症的患者在 D+180 时死亡;15 例中有 8 例(53%)死于 ADV。ADV 峰值 VL(风险比[HR],2.25;95%置信区间[CI],1.52-3.33)和增加的 AAUC(HR,2.95;95% CI,1.83-4.75)与 D+180 时的死亡率相关。
在 TCD HCT 中,ADV 峰值 VL 和 ADV AAUC 与 D+180 时的死亡率相关。我们的数据支持 ADV 病毒动力学作为 ADV 治疗临床试验终点的潜在效用。